When particles are entrained or dispersed in a flowing fluid, aggregation and/or agglomeration of the particles to form larger clumps is typically due to some attraction or adhesion between the particles or the addition of a flocculating agent that aids in attracting and aggregating the particles. Attractive forces between the particles may be ionic or physical entanglement. Some flocculating agents, such as chitosan, may also be directly attractive to the particles and thus form clumps of particles in the fluid medium.
Typically, after the clumps of particles are formed in the fluid medium, a physical filtration process is utilized to separate the aggregated, agglomerated, flocculated or otherwise process-formed particle clumps from the fluid. In a filter separation process, the physical filter media and the clumps of particles that have been separated from the fluid media are typically discarded, thus creating additional waste and increasing costs. Also, with the use of this physical filtration process, the yield of the filtrate is lessened, as some of it is used to saturate the filtering material. Further, as the filter fills up, filtration capacity is reduced, and the process is stopped to remove and replace the filter or otherwise remove the particles trapped thereon.
An example of this type of filtration is the filtering of a bioreactor to separate the cells and cell debris from the expressed products of the cells, such as monoclonal antibodies and recombinant proteins. In some applications, the filter process entails the use of a diatomaceous earth (DE) filter. The DE filters become filled quickly with the cellular waste from the bioreactor during the filtration process. This decreases the flux rate, the ability of the filter to trap materials and allow the fluid to pass through the filter, and increases the pressure differential between the material to be filtered and the post-filter material. As a result, some of the product from the bioreactor (monoclonal antibodies and recombinant proteins) is lost, thus decreasing the yield of the bioreactor. Also, any high pressure differential generated by the filter blockage can generate product damage.
Thus, methods are sought where continuous filtration may be carried out with little or no loss of the expressed monoclonal antibodies and recombinant proteins while separating most or all of the cells and cell debris that are in the bioreactor fluid. Such continuous methods would also be useful in other filtration applications such as the filtering of oil from water, components from blood, tailings from water in tailing ponds, and, generally, particles from a fluid stream and immiscible or emulsified fluids from a fluid stream.
Acoustophoresis is the separation of particles and secondary fluids from a primary or host fluid using acoustics, such as acoustic standing waves. It has been known that acoustic standing waves can exert forces on particles in a fluid when there is a differential in both density and/or compressibility, otherwise known as the acoustic contrast factor. The pressure profile in a standing wave contains areas of local minimum pressure amplitudes at standing wave nodes and local maxima at standing wave anti-nodes. Depending on their density and compressibility, the particles can be trapped at the nodes or anti-nodes of the standing wave. Generally, the higher the frequency of the standing wave, the smaller the particles that can be trapped.
At the MEMS (micro-electromechanical systems) scale, conventional acoustophoresis systems tend to use half or quarter wavelength acoustic chambers, which at frequencies of a few megahertz are typically less than a millimeter in thickness, and operate at very slow flow rates (e.g., μL/min). Such systems are not scalable since they benefit from extremely low Reynolds number, laminar flow operation, and minimal fluid dynamic optimization.
At the macro-scale, planar acoustic standing waves have been used in separation processes. However, a single planar wave tends to trap the particles or secondary fluid such that separation from the primary fluid is achieved by turning off the planar standing wave. The removal of the planar standing wave may hinder continuous operation. Also, the amount of power that is used to generate the acoustic planar standing wave tends to heat the primary fluid through waste energy, which may be disadvantageous for the material being processed.
Conventional acoustophoresis devices have thus had limited efficacy due to several factors including heat generation, use of planar standing waves, limits on fluid flow, and the inability to capture different types of materials. It would therefore be desirable to provide systems and methods for generating optimized particle clusters to improve gravity separation and collection efficiency. Improved acoustophoresis devices using improved fluid dynamics would also be desirable, as would making the acoustophoresis process continuous.